Development and optimization of curcumin analog nano-bilosomes using 2¹.3¹full factorial design for anti-tumor profiles improvement in human hepatocellular carcinoma:in-vitroevaluation,in-vivosafety assay

Abstract

Curcumin (CU) is a natural polyphenolic phytoingredient. CU has anti-inflammatory, anti-oxidant, and anticancer activities. The poor solubility, bioavailability, and stability of CU diminish its clinical application. Hence, structural modification of CU is highly recommended. The CU analog; 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one (PIP) exhibited high stability, safety, and more potent antiproliferative activity against hepatocellular carcinoma. In the present study, nano-bilosomes (BLs) were formulated to augment PIP delivery and enhance its solubility. A 2 1 .3 1 full factorial design was adopted to prepare the synthesized PIP-loaded BLs. Optimized F4 showed a biphasic release pattern extended over 24 h, with EE%, ZP, and PS of 90.21 ± 1.0%, −27.05 ± 1.08 mV, and 111.68 ± 1.4 nm. PIP-loaded BLs were tested for safety against a non-cancerous cell line (Wi-38) and for anticancer activity against the Huh-7 human hepatocellular carcinoma cells and compared to the standard anticancer drug doxorubicin (Dox). The anticancer selectivity index of PIP-loaded BLs recorded 420.55 against Huh-7 liver cancer cells, markedly higher than a CU suspension (18.959) or the Dox (20.82). The antiproliferative activity of nano-encapsulated PIP was roughly equivalent to Dox. PIP-loaded BLs, showed enhanced drug solubility, and enhanced anticancer effect, with lower toxicity and higher selectivity against Huh-7 liver cancer cells, compared to the parent CU.

Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells

“…It is worth noting that, although a negatively charged surface might slightly affect the cellular internalization, the stability of nano-systems against aggregation is crucial for benefiting from the nano-size. In addition, many studies have reported enhanced anticancer activity for negatively charged nanoformulation [ 44 , 45 , 46 , 47 ]. Accordingly, the study aimed at maximizing the absolute ZP value.…”

“…The reported size was sufficient for tumor-specific accumulation. Abbas et al reported an enhanced cytotoxic effect for optimized curcumin bilosomes with maximized negative absolute zeta potential of −27.05 mV [ 46 ]. On the other hand, previous studies that involve vesicles with higher size in the micro range exhibited low cytotoxicity profiles on different cell lines.…”

Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment

“…Natural plant drugs are used for anti-HCC treatment because of their low toxicity, but most of them have poor water solubility that limits their wide application. 185 Curcumin (CU) is an anti-inflammatory and anti-cancer natural polyphenolic plant component with enhanced solubility and anti-cancer effects, which was modified into nano vesicles by Abbas et al 186 Similarly, CU mitochondrial delivery system based on polyamide dendrimer molecules increase mitochondrial ROS levels and induce apoptosis at lower doses. 187 GA LPs interfere with various signaling proteins involved in HCC pathogenesis, altering.…”

Preparation and evaluation of the anti-cancer properties of RGD-modified curcumin-loaded chitosan/perfluorohexane nanocapsules in vitro

“…Curcumin (Cur) is a polyphenol that can be isolated from samples of turmeric root [ 1 ]. Prior research has demonstrated that Cur possesses a range of anti-tumor [ 2 , 3 ], anti-cancer [ 4 , 5 ], anti-inflammatory [ 6 ], antioxidant [ 7 ], and anti-ischemic [ 8 ] pharmacological properties. In the context of tumor treatment, Cur has been shown to be capable of inducing apoptotic tumor cell death inhibiting the proliferative and invasive activity of these cells [ 9 , 10 , 11 , 12 ].…”